Microfluidic Immunoassay for Enabling In Vivo Gastrointestinal Diagnostics

用于体内胃肠道诊断的微流控免疫分析

• 批准号: 8718216
• 负责人: Andrew J. Hilmer
• 金额: $ 4.99万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-09 至 2017-05-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8718216
• 关键词: Accounting; Acute myocardial infarction; Alkaline Phosphatase; Aminophenols; Bacteria; Biochemistry; Biological Assay; Biological Markers; Biomedical Engineering; Biopsy Specimen; Blood capillaries; Cardiac; Celiac Disease; Chemistry; Collaborations; Colorectal Cancer; Competitive Binding; Coupled; Detection; Development; Devices; Diagnostic; Dimensions; Discipline; Disease; Endoscopes; Endoscopic Biopsy; Endoscopy; Engineering; Enzyme-Linked Immunosorbent Assay; Future; Gastroenterology; Gastrointestinal Diseases; Gastrointestinal tract structure; Goals; Health; Hemoglobin; Hemorrhage; Human; Immunoassay; In Vitro; Individual; Inflammatory Bowel Diseases; Intestines; Knowledge; LMO2 gene; Lead; Lesion; Link; Liquid substance; Magnetic Resonance Imaging; Microfluidic Microchips; Microfluidics; Modeling; Modification; Molecular; Nanotechnology; Noise; One-Step dentin bonding system; Pain; Patients; Pattern; Process; Proteins; Radiology Specialty; Sampling; Serum; Signal Transduction; Simulate; Site; Solutions; Surface; System; Techniques; Technology; Testing; Training; Troponin I; Ultrasonography; Work; X-Ray Computed Tomography; antigen antibody binding; base; biological systems; capillary; capsule; career; design; gastrointestinal; imaging modality; in vivo; inorganic phosphate; miniaturize; minimally invasive; nanomaterials; point-of-care diagnostics; public health relevance; screening; sensor; skills; technological innovation

DESCRIPTION (provided by applicant): Pain Point and Proposed Solution: Gastrointestinal (GI) diseases, such as inflammatory bowel disease and colorectal cancer, would significantly benefit from protein-biomarker diagnostics at the site of a lesion. This is because conventional imaging methods such as ultrasound, MRI, and x-ray computed tomography cannot assess this molecular-level information. While immunoassay technologies are capable of quantifying disease biomarkers in vitro, current assay technologies are too large to be utilized for the assessment of gastrointestinal health, in vivo. Therefore, the objective of this project is to develop a miniaturized, diagnostics assay, which can be scaled down to capsule-sized dimensions. Technological Innovation: The initial microfluidic assay will focus on the detection of hemoglobin as a model biomarker for intestinal bleeding. The microfluidic device will be engineered to perform electrochemical immunoassays on a miniaturized scale within a fully autonomous microfluidic system. The specific aims of the project are the following: (1) Design an electrochemical ELISA for hemoglobin, and optimize under conditions that mimic intestinal fluid. (2) Design a miniaturized and autonomous microfluidic device, based on capillary- driven flow, for one-step detection of this protein biomarker. (3) Validate and optimize the platform using human intestinal fluid. Broader Impacts of the Technology: In the near-term, this platform could be coupled with an endoscope, allowing for direct analysis of the GI tract during endoscopy, or as a long-term objective, it could be incorporated into a capsule-based in vivo diagnostic device, allowing for periodic sampling of fluid along the gastrointestinal tract. This latter objective, in particular, could lead to a minimally invasive means of screening for a panel of gastrointestinal biomarkers, thereby providing a thorough assessment of gastrointestinal health for patients, and even healthy individuals. Further, as an immediately translational application, such a platform could be extended to point-of-care (POC) diagnostics involving serum-borne biomarkers, such as anti-TTG2 for celiac disease, or cardiac troponins I and T for acute myocardial infarction. Training Potential: The proposed training plan provides an opportunity for me to leverage my current scientific background in fluid dynamics, nanotechnology and sensor development, while expanding my skill set to include microfluidics, surface patterning and modification, device fabrication, and bioengineering - all of which will be essential for achieving my future career goal of leading an academic lab that utilizes nanomaterials to probe biological systems. In addition, the project provides a unique opportunity to work in collaboration with experts across a variety of fields, including biochemistry, bioengineering, microfluidics, gastroenterology, and radiology. Through these interactions, I will expand not only my breadth of knowledge, but also my academic network, building contacts across disciplines, and enabling future collaborations.

描述（由申请人提供）：痛点和建议的解决方案：胃肠道（GI）疾病，如炎症性肠病和结直肠癌，将显著受益于病变部位的蛋白质生物标志物诊断。这是因为传统的成像方法，如超声，MRI和X射线计算机断层扫描无法评估这种分子水平的信息。虽然免疫测定技术能够在体外定量疾病生物标志物，但目前的测定技术太大而不能用于体内胃肠道健康的评估。因此，本项目的目标是开发一种小型化的诊断分析方法，可以缩小到胶囊大小的尺寸。技术创新：最初的微流控检测将专注于检测 血红蛋白作为肠出血的模型生物标志物。微流体装置将被设计成在完全自主的微流体系统内以小型化的规模进行电化学免疫测定。本课题的具体目标如下：（1）设计血红蛋白的电化学ELISA方法，并在模拟肠液的条件下进行优化。(2)设计一种基于毛细管驱动流动的小型化和自主的微流体装置，用于这种蛋白质生物标志物的一步检测。(3)利用人体肠液对平台进行优化。该技术的更广泛影响：在短期内，该平台可以与内窥镜结合，允许在内窥镜检查期间直接分析胃肠道，或者作为长期目标，它可以被纳入基于胶囊的体内诊断设备，允许沿着胃肠道沿着定期采样液体。特别是后一个目标，可以导致一组胃肠道生物标志物的筛选的微创手段，从而为患者甚至健康个体提供胃肠道健康的全面评估。此外，作为立即转化的应用，这样的平台可以扩展到涉及血清携带的生物标志物的即时（POC）诊断，例如用于乳糜泻的抗TTG 2或用于急性心肌梗死的心肌肌钙蛋白I和T。培训潜力：拟议的培训计划为我提供了一个机会，利用我目前在流体动力学，纳米技术和传感器开发方面的科学背景，同时扩大我的技能，包括微流体，表面图案化和修饰，设备制造和生物工程-所有这些都将是实现我未来的职业目标所必需的，即领导一个利用纳米材料探测生物系统的学术实验室。此外，该项目还提供了一个独特的机会，与各个领域的专家合作，包括生物化学，生物工程，微流体，胃肠病学和放射学。通过这些互动，我将扩大不仅是我的知识广度，而且我的学术网络，跨学科建立联系，并使未来的合作。